Leonard Swinyer

Effectiveness of norgestimate and ethinyl estradiol in treating moderate acne vulgaris

BACKGROUND An excess of androgen is believed to contribute to development of acne in some patients. Because oral contraceptives (OCs) may reduce the active androgen level, hormonal therapy with OCs has been used successfully to treat patients with acne, although this treatment has previously not been studied in placebo-controlled trials. OBJECTIVE Our purpose was to evaluate the efficacy of a triphasic, combination OC (ORTHO TRI-CYCLEN [Ortho-McNeil Pharmaceutical, Raritan, N.J.], norgestimate/ethinyl estradiol) compared with placebo in the treatment of moderate acne vulgaris. METHODS Two hundred fifty-seven healthy female subjects, 15 to 49 years of age with moderate acne vulgaris, were enrolled in a multicenter, randomized, double-blind, placebo-controlled clinical trial. Each month for 6 months, subjects received either 3 consecutive weeks of the OC (i.e., tablets containing a fixed dose of ethinyl estradiol [0.035 mg] and increasing doses of norgestimate [0.180 mg, 0.215 mg, 0.250 mg]) followed by 7 days of inactive drug or placebo (color-matched tablets). Efficacy was assessed by facial acne lesion counts, an investigators global assessment, a subjects self-assessment, and an analysis of within-cycle variation (cycle 6) in lesion counts. RESULTS Of the 160 subjects in whom efficacy could be evaluated, the OC group showed a statistically significantly greater improvement than the placebo group for all primary efficacy measures. The mean decrease in inflammatory lesion count from baseline to cycle 6 was 11.8 (62.0%) versus 7.6 (38.6%) (p = 0.0001), and the mean decrease in total lesion count was 29.1 (53.1%) versus 14.1 (26.8%) (p = 0.0001) in the OC and placebo groups, respectively. In the investigators global assessment, 93.7% of the active treatment group versus 65.4% of the placebo group were rated as improved at the end of the study (p < 0.001). Six of the seven secondary efficacy measures (total comedones, open comedones, closed comedones, papules, pustules, and the subjects self-assessment of study treatment) were also significantly more favorable in the OC group compared with the placebo group. CONCLUSION An OC containing 0.035 mg of ethinyl estradiol combined with the triphasic regimen of norgestimate is a safe and effective treatment of moderate acne vulgaris in women with no known contraindication to OC therapy.

Tazarotene 0.1% gel plus corticosteroid cream in the treatment of plaque psoriasis.

Abstract Background: Topical corticosteroids are often used in the treatment of psoriasis, but long-term use may be associated with serious adverse events such as tachyphylaxis or atrophy of the skin. Tazarotene, a new topical retinoid, has demonstrated significant clinical benefits but can cause mild to moderate local irritation. Objective: We evaluate whether a combination treatment of topical tazarotene and a topical corticosteroid would increase efficacy while reducing the incidence of local adverse events associated with a topical retinoid. Methods: Three hundred patients enrolled in an investigator-masked study were randomly assigned to 1 of 4 treatment groups: tazarotene 0.1% gel in combination with placebo cream, or with a low-, mid-, or high-potency corticosteroid cream, for 12 weeks of treatment and a posttreatment follow-up at week 16. Results: Tazarotene 0.1% gel in combination with a mid- or high-potency corticosteroid, when compared with tazarotene plus placebo cream, achieved significantly greater reductions in scaling, erythema, and overall lesional severity, and a decreased incidence of adverse events. Conclusion: All tazarotene combinations (including tazarotene plus placebo) were highly effective in rapidly reducing the severity of psoriasis. Combining tazarotene with a topical corticosteroid increased efficacy while reducing the incidence of local adverse events. (J Am Acad Dermatol 1998;39:590-6.)

Efficacy and tolerability of combined topical treatment of acne vulgaris with adapalene and clindamycin: a multicenter, randomized, investigator-blinded study.

This multicenter, randomized, investigator-blinded study investigated the efficacy and tolerability of adapalene gel 0.1% plus clindamycin phosphate lotion 1%, compared with clindamycin plus vehicle for the treatment of mild to moderate acne vulgaris. A total of 249 patients applied clindamycin lotion twice daily and adapalene (125 patients) or vehicle gel (124 patients) once daily for 12 weeks. A significantly greater reduction of total (P <.001), inflammatory (P =.004) and noninflammatory lesions (P <.001) was seen in the clindamycin plus adapalene group than in the clindamycin plus vehicle group. These significant treatment effects were observed as early as week 4 for both noninflammatory and total lesion counts. Both treatment regimens were well tolerated. Although the worst scores for scaling (P <.05), dryness (P <.01), and stinging/burning (P <.05) were higher in the clindamycin plus adapalene group than in the clindamycin plus vehicle group in patients with moderate or severe irritation; in most cases these symptoms were of mild intensity.

Once-weekly fluconazole (450 mg) for 4, 6, or 9 months of treatment for distal subungual onychomycosis of the toenail

BACKGROUND Fluconazole is a bis-triazole antifungal agent approved for the treatment of oropharyngeal, esophageal, and vaginal candidiasis, serious systemic candidal infections, and cryptococcal meningitis. OBJECTIVE The purpose of this study was to evaluate three different durations of once-weekly fluconazole for the treatment of onychomycosis of the toenail caused by dermatophytes. METHODS In a multicenter, randomized, double-blind, parallel, placebo-controlled trial, 384 patients with distal subungual onychomycosis of the toenail received fluconazole, 450 mg once weekly, or placebo for 4, 6, or 9 months. For inclusion, patients were required to have mycologically confirmed distal subungual onychomycosis of the toenail with a large toenail at least 25% clinically affected but having at least 2 mm of healthy nail between the nail fold and the proximal onychomycotic border. Efficacy was assessed by clinical and mycologic (microscopic and microbiologic) measures at screening, at every treatment visit starting at month 3, and at months 2, 4, and 6 after therapy. Observed or volunteered adverse events were recorded and classified at all visits. RESULTS At the end of treatment, very significantly superior clinical and mycologic results were achieved in all fluconazole groups compared with placebo (p=0.0001). This superiority was largely maintained over 6 months of follow-up. The clinical and mycologic responses of the 9-month treatment duration were significantly superior to the 4- and 6-month durations. Similar percentages of patients in the fluconazole and placebo groups reported adverse experiences for all three durations of the study. CONCLUSION Results of this study support the efficacy and safety of fluconazole in the treatment of distal subungual onychomycosis of the toenail.

Patient‐reported outcomes from a multicenter, randomized, vehicle‐controlled clinical study of MAS063DP (Atopiclair™) in the management of mild‐to‐moderate atopic dermatitis in adults

Background: MAS063DP (Atopiclair™) is a topical cream approved for symptomatic relief in the treatment of atopic and contact dermatitis. Methods: This was a multicenter, randomized, double‐blind, vehicle‐controlled study in adults with mild–moderate atopic dermatitis. Patients were given MAS063DP or vehicle (2:1) three times per day to areas affected by atopic dermatitis for up to 50 days. A patient global assessment change from baseline was determined at days 8, 22, 36, and 50. Patient total body pruritus (visual analog scale) and patient opinion on treatment acceptability were also assessed. Results: A total of 218 patients (active: n = 145, vehicle: n = 73) were enrolled. At Day 22, 77% of patients on MAS063DP had a patient global assessment of good improvement or better versus 21% on vehicle (p<0.0001, chi‐squared test). Similarly, more patients had improvement in itch over their total body on MAS063DP than on vehicle (p<0.0001). Conclusion: MAS063DP treatment results in patient‐perceived improvements in mild–moderate atopic dermatitis.